The brain processes information and generates behavior by transmitting signals at its synapses, which connect neurons into vast networks of communicating cells. These networks, known as neural circuits, are not static but are modified throughout life by experience. Such neural circuit plasticity is critical for the brain to develop normally and perform all of its important functions, including learning and memory. When brain plasticity mechanisms function abnormally, however, devastating mental illnesses often ensue. Thus, a major goal of neuroscience research is to understand the detailed mechanisms by which the brain activity generated by experiences modifies neural circuit behavior. This occurs in large part because neural activity continually adjusts the efficiency or strength of synaptic communication between neurons, a process known as synaptic plasticity. Despite the importance of synaptic plasticity for brain development and higher brain functions, relatively litte is known about its molecular mechanisms other than it is commonly triggered by activity- dependent changes in intracellular calcium levels. This Conte Center will bring together four leading investigators to continue their previous efforts to use innovative molecular genetic manipulations combined with sophisticated and unique biochemical, electrophysiological, and imaging assays to elucidate highly novel mechanisms that underlie different forms of synaptic plasticity and how these forms of synaptic plasticity play a role in adaptive and pathological forms of experience-dependent plasticity, including learning and memory. The new insights into synaptic and circuit plasticity mechanisms generated by this Conte Center will influence a broad array of neuroscientists working on a wide range of topics related to normal and pathological brain function. The Center will also provide the research community with novel molecular genetic tools and genetically modified mice that can be used to manipulate proteins critical for synaptic plasticity throughout the brain to explore the roles of these critical proteins in specifi cell types that participate in a wide range of normal and pathological behaviors. Thus the Center will provide both technological and intellectual innovations to one of the most important areas of neuroscience research with far ranging implications for our understanding of normal and diseased brain function. Relevance The effectiveness of communication between nerve cells is modified by experience and these modifications are crucial for all normal brain functions including learning and memory. The goal of this Center is to determine the molecular mechanisms that are responsible for these modifications. Such information will lead to a better understanding of the causes of mental illness and eventually to the development of more efficacious treatments